European Urology Today: June/July 2023

patients with hypercalciuria due to its properties in lowering the excretion of calcium in urine. “No effects of HCT were observed in an intention-to-treat analysis, nor in the per-protocol analysis and neither on sensitive and subgroup analysis, with recurrence happening (49 - 59% across the four arms).” Nevertheless, the robust evidence currently available has been questioned by a group of researchers from Switzerland. They initiated the randomised clinical trial NOSTONE to investigate HCT’s efficacy in preventing recurrence in stone formers (defined as patients with at least two episodes of renal stones related events in the 10 years before recruitment), as well as to test the appropriate dose. The authors calculated a sample size of 416 patients randomised in four arms (1:1:1:1) comparing placebo vs HCT 12.5 mg vs HCT 25 mg vs HCT 50 mg (all once daily); the null hypothesis consisted in no-effect of HCT on the recurrence of renal stone, with the alternative hypothesis consisting in a dose effect according to a rank ordering. The recurrent event was defined by a composite outcome, including either a symptomatic (colic pain, stone passage, etc.) or radiological (at CT scan) recurrence of renal stone. Patients were recruited from March 2017 to October 2019 in 12 Swiss hospitals, and followed up for a mean of 2.9 years whilst taking the medication according to the assigned arm. Overall, no effects of HCT were observed in an intention-to-treat analysis, nor in the per-protocol analysis and neither on sensitive and subgroup analysis, with recurrence happening (49 - 59% across the four arms). Notably, patients with hypercalciuria accounted for 63% of the overall cohort of patients (range 59 - 66%). Therefore, the study could be considered underpowered for the

performed at a single academic research centre. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioural, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli. Participants attended two study visits at least seven days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate- matched placebo. Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioural measures of sexual desire and arousal. Of the 37 men randomised, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioural measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02). The investigators conclude that this trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioural measures of sexual desire and arousal. These data suggest that kisspeptin has

potential as the first pharmacological treatment for men with low sexual desire.

Prof. Francesco Sanguedolce Section editor Barcelona (ES)

Source: Effects of kisspeptin on sexual brain processing and penile tumescence in men with hypoactive sexual desire disorder: A randomised clinical trial. Mills EG, Ertl N, Wall MB, Thurston L, Yang L, Suladze S, Hunjan T, Phylactou M, Patel B, Muzi B, Ettehad D, Bassett PA, Howard J, Rabiner EA, Bech P, Abbara A, Goldmeier D, Comninos AN, Dhillo WS. JAMA Netw Open. 2023 Feb 1;6(2):e2254313. Trial registration: - Identifier: ISRCTN17271094. Hydrochlorothiazide and prevention of kidney-stone recurrence In the last 40 years, the advancements in the treatment for renal stones have mostly involved different ways to fragment renal stones via endoscopy, external lithotripsy, and multiple variants of minimally-invasive techniques. Medical drugs have never had a major role as none have been developed nor found to be effective in breaking stones (with the exception of the alkaline solution used to dissolve uric acid stones in specific situations) or better in preventing recurrence. The major reasons for the lack of medical advances in the management of renal stone patients include: 1. Complexity of the lithogenesis of the renal stones 2. Multiple factors that might intervene in the salts precipitation 3. Crystals formation 4. Stone growth Moreover, pharmaceutical companies in this medical field have little interest which also contributes to the lack of development of new molecules that could counter renal stone formation. As a result, among the most popular medical treatments used in urological practice is thiazide; specifically, hydrochlorothiazide (HCT). HCT is a very old diuretic agent recommended for years by international guidelines as a treatment option for


Prof. Oliver Reich Section editor Munich (DE)


Kisspeptin for men with hypoactive sexual desire disorder The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behaviour. The authors investigate the physiological, behavioural, neural, and hormonal effects of kisspeptin administration in men with HSDD. This double-blinded, two-way crossover, placebo- controlled randomised clinical trial was

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European Urology Today June/July 2023


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